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EORTC STBSG

EORTC STBSG. Predicting toxicity for patients with advanced Gastrointestinal Stromal Tumors (GIST) treated with imatinib mesylate : an EORTC/ISG/AGITG randomized trial.

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EORTC STBSG

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  1. EORTCSTBSG Predicting toxicity for patients with advanced Gastrointestinal Stromal Tumors (GIST) treated with imatinib mesylate : an EORTC/ISG/AGITG randomized trial M. Van Glabbeke, J. Verweij, P.G. Casali, J. Simes,A. Le Cesne, P. Reichardt, R. Issels, J.R. Judson,A.T. van Oosterom, J.-Y. Blay

  2. Material • Randomized phase III study comparing daily doses of imatinib (400 mg od vs 400 mg bid) for the treatment of patients with advanced GIST • 946 patients randomized • 942 patients started therapy • 310 patients still under therapy • Follow-up • Median: 42 months (3.5 years) • At 1, 2, 3 and 4 years: 99%, 90%, 81% and 4%

  3. Methods • Prognostic factors analyses • End-points (binary) : occurrence of • Grade 3-4 anemia, neutropenia • Grade 2-4 edema, fatigue, nausea, diarrhea, skin rash • Investigated co-factors • Imatinib dose • Age, sex, PS, baseline laboratory parameters • Time since GIST diagnosis, site of origin, lesion size • Prior therapies • Logistic univariate / multivariate regression models • Univariate model: select variables if P < 0.05 • Multivariate model: keep variable if P < 0.01

  4. Cumulative incidence of toxicities(non hemato.grade 2+, hemato. grade 3+) 400 mg o.d. 400 mg b.i.d. Edema - Skin rash - Fatigue - Nausea - Diarrhea Anemia - Neutropenia

  5. Multivariate models : non hematological grade 2+ toxicities ++ : P < 0.01, --- : P < 0.001, +++ : P < 0.001, ++++ : P < 0.0001

  6. Multivariate models : hematological grade 3+ toxicities -- : P < 0.01, ---- : P < 0.0001 , ++++ : P < 0.0001

  7. Interactive risk calculator www.eortc.be / tools / imatinibtoxicity • Interactive version • Downloads(Excel) • For PC • For PDA

  8. Interactive risk calculator for predictingimatinib toxicities in GIST patients

  9. Validation • Validation data set • EORTC phase I-II trial of imatinib • 91 patients with advanced or metastatic sarcoma • Daily doses: 400 mg, 600 mg, 800 mg, 1000 mg • Patients classified in “risk group” according to probability of each toxicity estimated with the model • < 20%, 20-40%, > 40% or < 20%, > 20% • Comparison with the observed proportion of events • Within the expected range for 10/13 risk groups (> 10 pts) • Overlap with the 95% confidence interval in all groups • Underestimation of edema & nausea (low risk groups) • Underestimation in male patients ?

  10. Conclusion (I) • All toxicities are highly dose dependent, except neutropenia • Anemia and neutropenia only depend on baseline hematological factors • Risk of non hematological toxicity increase with age, poor PS and in female • Confirmation of other series • Other factors • Prior chemotherapy (fatigue) • Small lesions (rash) • Identified GI origin (diarrhea)

  11. Conclusions (II) • Interactive risk calculator to estimate the risk of toxicity for individual patients • May be used in the clinic • Available on the internet (Excel spreadsheet) • May be used to customized treatment ? • Validation • Based on a limited data set • Underestimate of edema and nausea in male patients ? • Should be validated on larger data series

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